2021 Annual Report

Department of Structural Biology
Scientists in the Institute’s Department of Structural
Biology aim to understand the most basic building
blocks of biology to inform our understanding of
health and disease, and to aid in the development of
new, improved medications for an array of disorders.
Studying the foundations of life: VAI scientists
are investigating the mechanisms that allow our DNA
to replicate as well as the molecules at the core of
some of our most vital systems, such as temperature
regulation, communication between cells, and energy
production and regulation.
Turning weaknesses into strengths: VAI scientists
are investigating molecular vulnerabilities in bacteria,
such as those that cause tuberculosis and urinary tract
infections, and in diseases, such as cancer, to find ways
to leverage these weaknesses for treatment.
Aiding drug discovery: By better understanding
molecular structure and function, the work of VAI
scientists could aid in the development of more
targeted medications with fewer side effects.
2021 HIGHLIGHTS
A ‘tasty’ protein may lead to new ways to treat metabolic and immune diseases (Dr. Wei Lü and
Dr. Juan Du) — The same taste-sensing molecule that helps you enjoy a meal from your favorite restaurant may
one day lead to improved ways to treat diabetes and other metabolic and immune diseases. TRPM5 is a specialized
protein concentrated in the taste buds, where it helps relay messages to and from cells. It has long been of
interest to researchers due to its roles in taste perception and blood sugar regulation. VAI scientists
Dr. Wei Lü and Dr. Juan Du published the first-ever high-resolution images of TRPM5, which reveal two areas
that may serve as targets for new medications for diseases like diabetes. The structures also may aid in the
development of low-calorie alternative sweeteners that mimic sugar. 1
Fighting back against the bacteria that causes tuberculosis (Dr. Huilin Li) — Tuberculosis (TB) is
one of the top 10 causes of death worldwide, sickening 10 million people each year and claiming 1.5 million lives.
Although treatments exist, they can have side effects and must be taken consistently over several months.
VAI’s Dr. Huilin Li and his team are seeking out vulnerabilities in the bacteria that cause TB. They are studying the
microbes’ Pup-proteasome system, which the bacteria use to fend off attacks by the immune system so they can
survive inside immune cells and lie dormant for years.
Using the Institute’s powerful cryo-electron microscope (cryo-EM), Li and his team are developing detailed
blueprints of Pup-proteasome that can aid in the development of anti-TB medications. They also are investigating
several compounds that disable the bacterial Pup-proteasome system while sparing the infected person’s own
proteasome system, which plays crucial roles in health. 2,3
Funding Acknowledgements
Research reported in this publication was supported by:
1
Van Andel Institute; the National Heart, Lung, and Blood Institute of the National Institutes of Health under award nos. R56HL144929 (Lü) and R01HL153219 (Lü); a McKnight
Scholar Award (Du); a Klingenstein-Simons Scholar Award (Du); a Sloan Research Fellowship in neuroscience (Du); and a Pew Scholars in Biomedical Research Award from the
Pew Charitable Trusts (Du).
Lü also is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award no. R01NS112363 and by the National
Institute of General Medical Sciences of the National Institutes of Health under award no. R35GM138321. Du also is supported by the National Institute of Neurological
Disorders and Stroke of the National Institutes of Health under grant no. R01NS111031. Ruan is supported by an American Heart Association postdoctoral fellowship under
award no. 20POST35120556.
2
The National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award nos. R01AI143714 (Lin), R21144552 (Lin) and R01AI070285 (Li); the
Tri-Institutional Therapeutics Discovery Institute and Weill Cornell Medicine Matching Fund (Lin); and the Milstein Program in Translational Medicine. Kahne is supported
in part by the National Institute of Allergy and Infectious Disease under award no. T32AI007180.
3
The National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award nos. R01AI070285 (Li) and U19AI111143 (Glickman and Nathan); and
the National Cancer Institute under award no. P30CA008748 (Glickman).
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations.
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